Endothelial cells (ECs) are a key element of vasculature and are indispensable for repairing injured or ischemic tissues. Over the years, there have been may attempts to generate ECs for use in cell therapy. Despite early enthusiasm, adult stem or progenitor cells were found to have minimal endothelial transdifferentiation potential. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) emerged as promising alternatives; however, problems such as tumorigenic potential or inefficient cell production have limited their clinical application. Thus, there is a need to identify improved compositions and techniques.
Ginsberg et al. report reprogramming mature amniotic cells into endothelial cells by ETS factors and TGFβ suppression. Cell, 2012, 151:559-575. Direct conversion of lineage committed cells into ECs was reported through lentiviral overexpression of a combination of ETV2 (also known as ER71), ERG, and FLI1 with inhibition of TGFβ signaling. This method, however, utilized amniotic fluid-derived c-KIT negative cells as source cells, and reportedly did not work for postnatal cells. It is also unclear whether the source cells were fully differentiated, since their origin was amniotic tissues and potential contamination with stem or progenitor cells cannot be entirely excluded. Due to cell heterogeneity, clonal variability of the reprogrammed cells was noted as well.    Ieda et al. report reprogramming of fibroblasts into functional cardiomyocytes. Cell, 2010, 142:375-386.    Kurian et al. report conversion of human fibroblasts to angioblast-like progenitor cells. Nat Methods, 2013, 10:77-83.    Margariti et al. report reprogramming of fibroblasts into endothelial cells capable of angiogenesis and reendothelialization in tissue-engineered vessels. Proc Natl Acad Sci USA, 2012, 109:13793-13798.    Lee et al. report direct reprogramming of human dermal fibroblasts into endothelial cells using ETV2. Circulation, 2014, 130: A18205.    Morita et al. report ETV2 directly converts human fibroblasts into functional endothelial cells. Proc Natl Acad Sci USA, 2015, 112(1):160-165.    Liu et al. report induction of hematopoietic and endothelial cell program orchestrated by ETS transcription factor ER71/ETV2. EMBO reports (2015) embr.201439939.
References cited here are not an admission of prior art.